Gamboges, the resin from various Garcinia species including G. morella and G. hanburyi, is rich in anti-tumor gambogic acid (GA, CAS No. 2752-65-0) [1-7]. Gambogic acid was always isolated as an inseparable C(2) epimeric mixture whose structure could not be determined completely until the (R)-epimer was obtained by recrystallization of the pyridine salt of GA and identified by single crystal X-ray diffraction [8], [9]. As different epimers of the same compounds can have significantly different biological effects and different interactions with other therapeutic agents when used in combination, a common practice in chemotherapy, it is of great importance to be able to separate the epimers of the compounds naturally occuring in the herb gamboges that have anti-tumor effects.
Additionally, MDR in cancer cells is a significant factor for the failure of chemotherapy in many patients. It is very important to find and develop new anticancer drug that can overcome MDR of cancer cells, because MDR transporters contributed significantly to the pharmacokinetic disposition of anticancer drugs. Knowledge of substrates, inducers and inhibitors of these transporters is necessary to ensure optimal clinical outcomes [10]. In addition, chemotherapy often requires multidrug combination, and most anti-cancer drugs are metabolic substrates of cytochrome P450s. Therefore, understanding of drug-drug interactions is important for the combination use of anti-cancer drugs. The likelihood of drug interactions with combination therapy will be very high, if these combined drugs are substrates and potent inhibitors or inducers of the cytochrome P450 (CYP) system [11].